Effects of nitric oxide and peroxynitrite on the cytochrome oxidase K-m for oxygen: implications for mitochondrial pathology

This review summarises current knowledge about the effect of oxygen on cyto chrome oxidase activity in vitro and in vivo. Cytochrome oxidase normally o perates above its K-m for oxygen in vivo. However, decreases in the intrace llular oxygen concentration (hypoxia) under physiological extremes, or duri ng pathophysiology, can cause mitochondrial respiration to become oxygen li mited. Inhibitors that raise the enzyme's K-m will induce oxygen limitation under apparently normoxic conditions. It is known that the concentrations of nitric oxide and peroxynitrite are raised in a number of pathophysiologi cal conditions. These compounds are capable of reversibly and irreversibly raising the cytochrome oxidase K-m for oxygen. Therefore, measurements of c ell and mitochondrial respiration in vitro that fail to systematically vary oxygen through the range of physiological concentrations are likely to und erestimate the effects of nitric oxide and peroxynitrite in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.